Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice
Alveolar macrophages (AMs) are differentially regulated by human surfactant protein-A1 (SP-A1) or SP-A2. However, AMs are very heterogeneous and differences are difficult to characterize in intact cells. Using the Toponome Imaging System (TIS), an imaging technique that uses sequential immunostainin...
| Những tác giả chính: | , , , , , , |
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| Định dạng: | Bài viết |
| Ngôn ngữ: | English |
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American Society for Clinical investigation
2020-12-01
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| Loạt: | JCI Insight |
| Những chủ đề: | |
| Truy cập trực tuyến: | https://doi.org/10.1172/jci.insight.141410 |
| _version_ | 1831584637244145664 |
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| author | David S. Phelps Vernon M. Chinchilli Judith Weisz Lili Yang Debra Shearer Xuesheng Zhang Joanna Floros |
| author_facet | David S. Phelps Vernon M. Chinchilli Judith Weisz Lili Yang Debra Shearer Xuesheng Zhang Joanna Floros |
| author_sort | David S. Phelps |
| collection | DOAJ |
| description | Alveolar macrophages (AMs) are differentially regulated by human surfactant protein-A1 (SP-A1) or SP-A2. However, AMs are very heterogeneous and differences are difficult to characterize in intact cells. Using the Toponome Imaging System (TIS), an imaging technique that uses sequential immunostaining to identify patterns of biomarker expression or combinatorial molecular phenotypes (CMPs), we studied individual single cells and identified subgroups of AMs (n = 168) from SP-A–KO mice and mice expressing either SP-A1 or SP-A2. The effects, as shown by CMPs, of SP-A1 and SP-A2 on AMs were significant and differed. SP-A1 AMs were the most diverse and shared the fewest CMPs with KO and SP-A2. Clustering analysis of each group showed 3 clusters where the CMP-based phenotype was distinct in each cluster. Moreover, a clustering analysis of all 168 AMs revealed 10 clusters, many dominated by 1 group. Some CMP overlap among groups was observed with SP-A2 AMs sharing the most CMPs and SP-A1 AMs the fewest. The CMP-based patterns identified here provide a basis for understanding not only AMs’ diversity, but also most importantly, the molecular basis for the diversity of functional differences in mouse models where the impact of genetics of innate immune molecules on AMs has been studied. |
| first_indexed | 2024-12-17T21:03:07Z |
| format | Article |
| id | doaj.art-0b47d4f51d2944de83b5cf75390c6f2f |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-17T21:03:07Z |
| publishDate | 2020-12-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-0b47d4f51d2944de83b5cf75390c6f2f2022-12-21T21:32:39ZengAmerican Society for Clinical investigationJCI Insight2379-37082020-12-01524Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic miceDavid S. PhelpsVernon M. ChinchilliJudith WeiszLili YangDebra ShearerXuesheng ZhangJoanna FlorosAlveolar macrophages (AMs) are differentially regulated by human surfactant protein-A1 (SP-A1) or SP-A2. However, AMs are very heterogeneous and differences are difficult to characterize in intact cells. Using the Toponome Imaging System (TIS), an imaging technique that uses sequential immunostaining to identify patterns of biomarker expression or combinatorial molecular phenotypes (CMPs), we studied individual single cells and identified subgroups of AMs (n = 168) from SP-A–KO mice and mice expressing either SP-A1 or SP-A2. The effects, as shown by CMPs, of SP-A1 and SP-A2 on AMs were significant and differed. SP-A1 AMs were the most diverse and shared the fewest CMPs with KO and SP-A2. Clustering analysis of each group showed 3 clusters where the CMP-based phenotype was distinct in each cluster. Moreover, a clustering analysis of all 168 AMs revealed 10 clusters, many dominated by 1 group. Some CMP overlap among groups was observed with SP-A2 AMs sharing the most CMPs and SP-A1 AMs the fewest. The CMP-based patterns identified here provide a basis for understanding not only AMs’ diversity, but also most importantly, the molecular basis for the diversity of functional differences in mouse models where the impact of genetics of innate immune molecules on AMs has been studied.https://doi.org/10.1172/jci.insight.141410ImmunologyPulmonology |
| spellingShingle | David S. Phelps Vernon M. Chinchilli Judith Weisz Lili Yang Debra Shearer Xuesheng Zhang Joanna Floros Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice JCI Insight Immunology Pulmonology |
| title | Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice |
| title_full | Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice |
| title_fullStr | Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice |
| title_full_unstemmed | Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice |
| title_short | Differences in the alveolar macrophage toponome in humanized SP-A1 and SP-A2 transgenic mice |
| title_sort | differences in the alveolar macrophage toponome in humanized sp a1 and sp a2 transgenic mice |
| topic | Immunology Pulmonology |
| url | https://doi.org/10.1172/jci.insight.141410 |
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